The process of normal labor in humans represents a type of inflammatory response. Many of the cellular and biochemical mediators of inflammation elicit specific responses in the quiescent uterus, the cervix and the fetal membranes1. As part of this process, leukocytes infiltrate the myometrium2, the cervix3 and the fetal membranes3,4. These leukocytes, along with the resident cells of the reproductive tissues secrete inflammatory mediators including cytokines, matrix metalloproteinases (MMPs), and prostaglandins (PGs), which participate in the regulation of the events of labor1,5.
It has been proposed that specific leukocyte subsets infiltrate the fetal membranes around the time of labor, creating an inflammatory microenvironment and secreting mediators which may allow the final rupture of these tissues3,6. Regarding to the phenotype of the infiltrated leukocytes in the fetal membranes before and at the parturition time, it has been reported that they generally consisting of granulocytes, T cells and a lesser proportion of monocytes.
Leukocyte recruitment and homing are regulated by specific mediators and generally occur in sequential steps. First, tissues secrete chemokines which are the soluble mediators that are responsible for the selective recruitment of leukocytes to a particular tissue8. Once they have arrived at the tissue, leukocytes express cell adhesion molecules (CAMs) which allow them to adhere to the vascular endothelium and subsequently to extravasate from the blood vessel and into the tissue9. In the reproductive tissues, it has been demonstrated that chemokines recruit specific leukocyte subsets before and during labor6,10.
Preterm delivery is the largest contributor to perinatal mortality and morbidity with long term consequences and tremendous personal and societal costs. In Alberta, the preterm birth rate is >9%, and in the USA it is >12%, of all pregnancies.
Currently, the best predictor of preterm birth is considered to be whether the mother has had a previous preterm pregnancy. A mother has approximately a 15% chance of delivering the next baby preterm as well. If the mother has had two previous preterm pregnancies, the predictability for the current pregnancy doubles to about 30%.
If a mother was preterm herself, or if her first or second degree relatives had preterm births, the risk of preterm birth is increased.
Twin studies estimate an overall heritability from 15% to 40%.
Presently, there is no reliable test of any kind that predicts women at risk of preterm delivery.
The only pregnancy test on the market is the fetal fibronectin test from Hologic in which a cervical swab can be tested for the presence of fetal fibronectin. This is used as a test to predict pregnancy maintenance and does not predict preterm birth or pregnancy termination. It selects for the women not to treat, but does not select for those who should be treated.
It is, therefore, desirable to provide compositions, methods and/or kits for determining the likelihood of developing a disorder of pregnancy, such as preterm delivery.
This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should it be construed, that any of the preceding information constitutes prior art against the present invention.